Sarcolemmal and mitochondrial K-ATP channels mediate cardioprotection in chronically hypoxic hearts

Hypoxia from birth increases the resistance of the isolated neonatal heart to ischemia. We determined if increased resistance to ischemia was due to a ctivation of sarcolemmal or mitochondrial K channels. Rabbits (n=8/group) w ere raised from birth in a normoxic (F1O2 = 0.21) or hypoxic (F1O2 = 0.12) environment for 8-10 days and the heart perfused with Krebs-Henscleit bicar bonate buffer. A mitochondrial-selective K-ATP, channel blocker 5-hpdroxyde canoate (5-HD) (300 mu mol/l) or a sarcolcmmal-selective K-ATP, channel blo cker HMR 1098 ( 30 mu mol/l) were added alone or in combination for 20 min prior to a global ischemic period of 30 min. followed by 35 min reperfusion . Recovery of ventricular developed pressure R as higher in chronically hyp oxic than normoxic hearts. 5-HD and HMR 1098 partially reduced the cardiopr otective effect of chronic hypoxia, but had no effect in normoxic hearts. T he combination of 5-HD and HMR 1098 abolished the cardioprotective effect o f chronic hypoxia. We conclude that both sarcolemmal and mitochondrial K-AT P channels contribute to cardioprotection in the chronically hypoxic heart. (C) 2001 Academic Press.